PI-103 reduces UCH-1 proliferation and induces apoptosis by inhibiting the PI3K / mTOR pathway.[39] Interestingly, although the Rap1 signaling pathway has not been shown to be associated with chordoma, Sitong Zhou recently demonstrated that SHARPIN promotes melanoma migration and invasion by regulating Rap1 and its downstream pathways (including p38 and JNK/c-jun) by activating the Rap1 signaling pathway.[40]. The gene discussed is JUN; the disease is melanoma.